Did viruses help make us human? As weird as it sounds, the question is actually a reasonable one to ask. And now scientists have offered some evidence that the answer may be yes.

If you’re sick right now with the flu or a cold, the viruses infecting you are just passing through. They invade your cells and make new copies of themselves, which burst forth and infect other cells. Eventually your immune system will wipe them out, but there’s a fair chance some of them may escape and infect someone else.

But sometimes viruses can merge into our genomes. Some viruses, for example, hijack our cells by inserting its genes into our own DNA. If they happen to slip into the genome of an egg, they can potentially get a new lease on life. If the egg is fertilized and grows into an embryo, the new cells will also contain the virus’s DNA. And when that embryo becomes an adult, the virus has a chance to move into the next generation.

These so-called endogenous retroviruses are sometimes quite dangerous. Koalas, for example, are suffering from a devastating epidemic of them. The viruses are spreading both on their own from koala to koala and from parents to offspring. As the viruses invade new koala cells, they sometimes wreak havoc on their host’s DNA. If a virus inserts itself in the wrong place in a koala cell, it may disrupt its host’s genes. The infected cell may start to grow madly, and give rise to cancer.

If the koalas manage to survive this outbreak, chances are that the virus will become harmless. Their immune systems will stop their spread from one host to another, leaving only the viruses in their own genomes. Over the generations, mutations will erode their DNA. They will lose the ability to break out of their host cell. They will still make copies of their genes, but those copies will only get reinserted back into their host’s genome. But eventually they will lose even this feeble ability to replicate.

We know this is the likely future of the koala retroviruses, because we can see it in ourselves. Viruses invaded the genomes of our ancestors several times over the past 50 million years or so, and their viral signature is still visible in our DNA. In fact, we share many of the same stretches of virus DNA with apes and monkeys. Today we carry half a million of these viral fossils, which make up eight percent of the human genome. (Here are some posts I’ve written about endogenous retroviruses.)

But proteins aren’t the only potentially useful parts that we can harvest from our viruses.

Many human genes are accompanied by tiny stretches of DNA called enhancers. When certain proteins latch onto the enhancer for a gene, they start speeding up the productions of proteins from it. Viruses that infect us have enhancers, too. But instead of causing our cells to make more of our own proteins, these virus enhancers cause our cells to make more viruses.

But what happens when a virus’s enhancer becomes a permanent part of the human genome? Recently a team of scientists carried out a study to find out. They scanned the human genome for enhancers from the youngest endogenous retroviruses in our DNA. These viruses, called human-specific endogenous retroviruses, infected our ancestors at some point after they split off from chimpanzees some seven million years ago. We know this because these viruses are in the DNA of all living people, but missing from other primates.

Once the scientists had cataloged these virus enhancers, they wondered if any of them were now enhancing human genes, instead of the genes of viruses. If that were the case, these harnessed enhancers would need to be close to a human gene. The scientists found six such enhancers.

Of these six enhancers, however, only one showed signs of actually boosting the production of the nearby gene. Known as PRODH, it encodes an enzyme that’s involved in making signaling molecules in the brain. And if the enzyme isn’t working properly, the brain can go awry.

In 1999, scientists shut down the PRODH gene in mice and found a striking change in their behavior. They ran an experiment in which they played a loud noise to the mice at random times. Then they started playing a soft tone just before the noise. Normal mice learn to connect the two sounds, and they become less startled by the loud noise. But mice without PRODH remained as startled as ever.

Other researchers have also found evidence for the importance of PRODH in the human brain. In some studies, mutations to the gene have been linked to schizophrenia, for example. (One study has failed to find that link, though.) A mutation that deletes the PRODH gene and its surrounding DNA has been linked to a rare psychiatric disorder, called DiGeorge syndrome.

Once the scientists had found the virus enhancer near PRODH, they took a closer look at how they work in human cells. As they report in the Proceedings of the National Academy of Sciences this week, they searched for the activity of PRODH in tissue from human autopsies. PRODH is most active in the brain–and most active in a few brain regions in particular, such as the hippocampus, which organizes our memories.

The new research suggests that the virus enhancer is partly responsible for PRODH becoming active where it does. Most virus enhancers in our genome are muzzled with molecular caps on our DNA. That’s probably a defense to keep our cells from making proteins willy-nilly. But the hippocampus and other regions of the brain where PRODH levels are highest, the enhancer is uncapped. It may be left free to boost the PRODH gene in just a few places in the brain.

The scientists also found one protein that latches onto the virus enhancer, driving the production of PRODH proteins. And in a striking coincidence, that protein, called SOX2, is also produced at high levels in the hippocampus.

What makes all this research all the more provocative is that this situation appears to be unique to our own species. Chimpanzees have the PRODH gene, but they lack the virus enhancer. They produce PRODH at low levels in the brain, without the intense production in the hippocampus.

Based on this research, the scientists propose a scenario. Our ancestors millions of years ago were infected with a virus. Eventually it became lodged in our genome. At some point, a mutation moved the virus enhancer next to the PRODH gene. Further mutations allowed it to helped boost the gene’s activity in certain areas of the brain, such as the hippocampus.

The scientists can’t say how this change altered the human brain, but given what we know about brain disorders linked to the PRODH gene, it could have been important.

It’s always important approach studies on our inner viruses with some skepticism. Making a compelling case that a short stretch of DNA has an important function takes not just one experiment, but a whole series of them. And even if this enhancer does prove to have been one important step in the evolution of the human brain, our brains are also the result of many other mutations of a far more conventional sort.

Still, the intriguing possibility remains. Perhaps our minds are partly the way they are today thanks to an infection our ancestors got a few millions of years ago.

Related

10 thoughts on “How Our Minds Went Viral”

Just as we discovered that many bacteria and other microorganisms were beneficial, I would expect eventual discovery of numerous beneficial viruses. Viruses also offer a channel of communication, perhaps complex, between cells, in parallel with the exchange of genetic material and other signaling substances.

Hmmm, yes, what do we know of the origin of viruses? Perhaps they were functioning parts of other organisms, but some became semi-independent. What look like traces of past invasions would then actually be more like scars, the remains of a lost system of environmental sensing and adaptation.

Anarcissie, Carl wrote about the “Inner Lions” in an earlier blog. Some viruses serve to keep bacteria in check that would otherwise cause us harm. So there’s no doubt that there are beneficial viruses (even if they are just greedily looking for food and not behaving that way strictly for our benefit)

Cristy Gelling ,
No , all genomes have PRODH gene ,,, but the enhancers which increases the “PRODH” enzyme production are due to an infection which our ancestor had in the past.. The mice in this sentence are the one who don’t have the PRODH enhancers …

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